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Osimertinib: A Review in T790M-Positive Advanced Non-Small Cell Lung Cancer

  • Adis Drug Evaluation
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Abstract

Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis. PFS results were consistent across predefined subgroups of patients, including those with CNS metastases at baseline. There was no difference between treatment groups in overall survival at 26% maturity. Objective response rates (ORRs) and patient-reported outcomes for prespecified symptoms were also significantly improved with osimertinib relative to platinum-pemetrexed, with CNS ORRs in patients with CNS metastases more than twofold higher in the osimertinib than in the platinum-pemetrexed group. Osimertinib had a manageable tolerability profile, with relatively few patients permanently discontinuing treatment because of adverse events (AEs). With limited treatment options available in this setting, osimertinib is an important option in adult patients with advanced EGFR T790M-positive NSCLC.

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Acknowledgments

During the peer review process, the manufacturer of osimertinib was offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Yvette N. Lamb & Lesley J. Scott

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  1. Yvette N. Lamb
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  2. Lesley J. Scott
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Corresponding author

Correspondence to Yvette N. Lamb.

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Funding

The preparation of this review was not supported by any external funding.

Conflicts of Interest

Yvette Lamb and Lesley Scott are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Disclosures

Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/3E48F060327EBA8E.

Additional information

The manuscript was reviewed by: V. Hirsh, Department of Medical Oncology, McGill University Health Centre, Montreal, Canada; K. Leventakos, Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA; A. Morabito, Medical Oncology Unit, Thoraco-Pulmonary Department, Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy; M. Scheffler , Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Cologne, Bonn, Cologne, Germany; J. Subramanian , St Luke’s Cancer Institute, Kansas City, MO, USA.

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Lamb, Y.N., Scott, L.J. Osimertinib: A Review in T790M-Positive Advanced Non-Small Cell Lung Cancer. Targ Oncol 12, 555–562 (2017). https://doi.org/10.1007/s11523-017-0519-0

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  • DOI: https://doi.org/10.1007/s11523-017-0519-0

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